A Pilot, Single Arm, Prospective Trial Using Neoadjuvant Rapamycin Prior To Definitive Therapy In Head And Neck Squamous Cell Carcinoma

6071 Background: Deregulated PI3K-AKT-mTOR signaling is one of the most common abnormalities in head and neck squamous cell carcinoma (HNSCC). We previously showed that mTOR inhibition with rapamycin significantly inhibited the growth of human HNSCC xenografts and oral cancers in multiple genetically-defined and chemically-induced mouse models. A pilot trial of neoadjuvant rapamycin treatment was developed to assess its effect on clinical response and mTOR signaling. Methods: Patients with untreated stage II-IVA HNSCC received 21 days of rapamycin treatment (15 mg on day 1, 5 mg on days 2-21) prior to definitive treatment with surgery or chemoradiation. Treatment responses were assessed clinically and radiographically with CT and FDG-PET. Pre- and post-treatment biopsies and blood were obtained for toxicity, immune monitoring and immunohistochemical assessment of mTOR signaling. Results: Sixteen patients (8 oral cavity, 8 oropharyngeal) completed rapamycin and definitive treatment (15-surgery, 1-chemoradi...